Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: Evidence for susceptibility loci on 1q

Josée Dupuis; Martin G. Larson; Ramachandran S. Vasan; Joseph M. Massaro; Peter W.F. Wilson; Izabella Lipinska; Diane Corey; Joseph A. Vita; John F. Keaney; Emelia J. Benjamin

doi:10.1016/j.atherosclerosis.2005.02.015

Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: Evidence for susceptibility loci on 1q

Josée Dupuis, Martin G. Larson, Ramachandran S. Vasan, Joseph M. Massaro, Peter W.F. Wilson, Izabella Lipinska, Diane Corey, Joseph A. Vita, John F. Keaney, Emelia J. Benjamin

Research output: Contribution to journal › Article › peer-review

90 Scopus citations

Abstract

Vascular inflammation plays a central role in atherosclerosis and inflammatory biomarkers predict risk of cardiovascular disease (CVD). Thus, finding genes that influence systemic levels of inflammatory biomarkers may provide insights into genetic determinants of vascular inflammation and CVD. We conducted variance-component linkage analyses of blood levels of four biomarkers of vascular inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1)] in 304 extended families from the Framingham Heart Study, using data from a 10 cM genome scan. We computed p-values by a permutation approach. Heritability estimates ranged from 14% (IL-6) to 44% (MCP-1) after log transforming and adjusting for covariates. Significant linkage to MCP-1 was found on chromosome 1 (LOD = 4.27 at 186 cM; genome-wide p = 0.005), in a region containing inflammatory candidate genes such as SELE, SELP (E- and P-selectin) and CRP. Other linkage peaks with LOD scores >2 were found for MCP-1 on chromosome 1 (LOD = 2.04 at 16 cM; LOD = 2.34 at 70 cM) and chromosome 17 (LOD = 2.44 at 22 cM) and for sICAM-1 on chromosome 1 at 229 cM (LOD = 2.09) less than 5 cM from the interleukin-10 (IL10) gene. Multiple genes on chromosome 1 may influence inflammatory biomarker levels and may have a potential role in development of CVD.

Original language	English (US)
Pages (from-to)	307-314
Number of pages	8
Journal	Atherosclerosis
Volume	182
Issue number	2
DOIs	https://doi.org/10.1016/j.atherosclerosis.2005.02.015
State	Published - Oct 2005
Externally published	Yes

Keywords

Cardiovascular diseases
Epidemiology
Genetics
Inflammation
Risk factors

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

Access to Document

10.1016/j.atherosclerosis.2005.02.015

Cite this

Dupuis, J., Larson, M. G., Vasan, R. S., Massaro, J. M., Wilson, P. W. F., Lipinska, I., Corey, D., Vita, J. A., Keaney, J. F., & Benjamin, E. J. (2005). Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: Evidence for susceptibility loci on 1q. Atherosclerosis, 182(2), 307-314. https://doi.org/10.1016/j.atherosclerosis.2005.02.015

@article{6d66666b119947ed8cb049c93fcde8bd,

title = "Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: Evidence for susceptibility loci on 1q",

abstract = "Vascular inflammation plays a central role in atherosclerosis and inflammatory biomarkers predict risk of cardiovascular disease (CVD). Thus, finding genes that influence systemic levels of inflammatory biomarkers may provide insights into genetic determinants of vascular inflammation and CVD. We conducted variance-component linkage analyses of blood levels of four biomarkers of vascular inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1)] in 304 extended families from the Framingham Heart Study, using data from a 10 cM genome scan. We computed p-values by a permutation approach. Heritability estimates ranged from 14% (IL-6) to 44% (MCP-1) after log transforming and adjusting for covariates. Significant linkage to MCP-1 was found on chromosome 1 (LOD = 4.27 at 186 cM; genome-wide p = 0.005), in a region containing inflammatory candidate genes such as SELE, SELP (E- and P-selectin) and CRP. Other linkage peaks with LOD scores >2 were found for MCP-1 on chromosome 1 (LOD = 2.04 at 16 cM; LOD = 2.34 at 70 cM) and chromosome 17 (LOD = 2.44 at 22 cM) and for sICAM-1 on chromosome 1 at 229 cM (LOD = 2.09) less than 5 cM from the interleukin-10 (IL10) gene. Multiple genes on chromosome 1 may influence inflammatory biomarker levels and may have a potential role in development of CVD.",

keywords = "Cardiovascular diseases, Epidemiology, Genetics, Inflammation, Risk factors",

author = "Jos{\'e}e Dupuis and Larson, {Martin G.} and Vasan, {Ramachandran S.} and Massaro, {Joseph M.} and Wilson, {Peter W.F.} and Izabella Lipinska and Diane Corey and Vita, {Joseph A.} and Keaney, {John F.} and Benjamin, {Emelia J.}",

note = "Funding Information: From the NHLBI's Framingham Heart Study, supported by NIH/NHLBI N01-HC-25195 and N01-HV-28178; NIH grants HL64753 & HL76784-01(EJB), DK55656 (JFK), HL70139 (RSV) and HL60886 (JAV and JFK). Dr. Keaney is an American Heart Association Established Investigator. Dr. Vasan a National Institute of Health Research Career Award Recipient (HL04334). We thank Qiong Yang and Larry Atwood for computing assistance and Moira Pryde for reference collection. ",

year = "2005",

month = oct,

doi = "10.1016/j.atherosclerosis.2005.02.015",

language = "English (US)",

volume = "182",

pages = "307--314",

journal = "Atherosclerosis",

issn = "0021-9150",

publisher = "Elsevier Ireland Ltd",

number = "2",

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TY - JOUR

T1 - Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study

T2 - Evidence for susceptibility loci on 1q

AU - Dupuis, Josée

AU - Larson, Martin G.

AU - Vasan, Ramachandran S.

AU - Massaro, Joseph M.

AU - Wilson, Peter W.F.

AU - Lipinska, Izabella

AU - Corey, Diane

AU - Vita, Joseph A.

AU - Keaney, John F.

AU - Benjamin, Emelia J.

N1 - Funding Information: From the NHLBI's Framingham Heart Study, supported by NIH/NHLBI N01-HC-25195 and N01-HV-28178; NIH grants HL64753 & HL76784-01(EJB), DK55656 (JFK), HL70139 (RSV) and HL60886 (JAV and JFK). Dr. Keaney is an American Heart Association Established Investigator. Dr. Vasan a National Institute of Health Research Career Award Recipient (HL04334). We thank Qiong Yang and Larry Atwood for computing assistance and Moira Pryde for reference collection.

PY - 2005/10

Y1 - 2005/10

N2 - Vascular inflammation plays a central role in atherosclerosis and inflammatory biomarkers predict risk of cardiovascular disease (CVD). Thus, finding genes that influence systemic levels of inflammatory biomarkers may provide insights into genetic determinants of vascular inflammation and CVD. We conducted variance-component linkage analyses of blood levels of four biomarkers of vascular inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1)] in 304 extended families from the Framingham Heart Study, using data from a 10 cM genome scan. We computed p-values by a permutation approach. Heritability estimates ranged from 14% (IL-6) to 44% (MCP-1) after log transforming and adjusting for covariates. Significant linkage to MCP-1 was found on chromosome 1 (LOD = 4.27 at 186 cM; genome-wide p = 0.005), in a region containing inflammatory candidate genes such as SELE, SELP (E- and P-selectin) and CRP. Other linkage peaks with LOD scores >2 were found for MCP-1 on chromosome 1 (LOD = 2.04 at 16 cM; LOD = 2.34 at 70 cM) and chromosome 17 (LOD = 2.44 at 22 cM) and for sICAM-1 on chromosome 1 at 229 cM (LOD = 2.09) less than 5 cM from the interleukin-10 (IL10) gene. Multiple genes on chromosome 1 may influence inflammatory biomarker levels and may have a potential role in development of CVD.

AB - Vascular inflammation plays a central role in atherosclerosis and inflammatory biomarkers predict risk of cardiovascular disease (CVD). Thus, finding genes that influence systemic levels of inflammatory biomarkers may provide insights into genetic determinants of vascular inflammation and CVD. We conducted variance-component linkage analyses of blood levels of four biomarkers of vascular inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1)] in 304 extended families from the Framingham Heart Study, using data from a 10 cM genome scan. We computed p-values by a permutation approach. Heritability estimates ranged from 14% (IL-6) to 44% (MCP-1) after log transforming and adjusting for covariates. Significant linkage to MCP-1 was found on chromosome 1 (LOD = 4.27 at 186 cM; genome-wide p = 0.005), in a region containing inflammatory candidate genes such as SELE, SELP (E- and P-selectin) and CRP. Other linkage peaks with LOD scores >2 were found for MCP-1 on chromosome 1 (LOD = 2.04 at 16 cM; LOD = 2.34 at 70 cM) and chromosome 17 (LOD = 2.44 at 22 cM) and for sICAM-1 on chromosome 1 at 229 cM (LOD = 2.09) less than 5 cM from the interleukin-10 (IL10) gene. Multiple genes on chromosome 1 may influence inflammatory biomarker levels and may have a potential role in development of CVD.

KW - Cardiovascular diseases

KW - Epidemiology

KW - Genetics

KW - Inflammation

KW - Risk factors

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U2 - 10.1016/j.atherosclerosis.2005.02.015

DO - 10.1016/j.atherosclerosis.2005.02.015

M3 - Article

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AN - SCOPUS:24044536902

SN - 0021-9150

VL - 182

SP - 307

EP - 314

JO - Atherosclerosis

JF - Atherosclerosis

IS - 2

ER -

Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: Evidence for susceptibility loci on 1q

Abstract

Keywords

ASJC Scopus subject areas

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